Expression of H-Y antigen in females appears to correlate with ovarian failure. Initially this anomalous expression of H-Y was attributed to varying degrees of sex chromosomal anomalies. However, apparently normal XX women with amenorrhea and aged female mice past the average reproductive age have also been typed H-Y+ with our monoclonal H-Y specific antibodies. We propose that changes in hormonal levels known to occur with ovarian failure, e.g., decrease in estrogens and precipitous rise in the gonadotrophins FSH and LH, influence the expression of H-Y. We intend to: 1) identify the cause of anomalous expression of H-Y antigen in females by using mouse models to correlate expression of H-Y with ovarian morphology and hormonal levels, 2) conduct a clinical evaluation of H-Y typing in women with emphasis on karyotypic and hormonal analyses, and 3) develop a monoclonal anti-idiotype antibody to H-Y antibody for an improved H-Y typing assay. Our primary objective is to gain understanding of anomalous H-Y expression in women. Our long term objective is to establish H-Y typing as a clinical test to pinpoint women at risk for ovarian failure.